Hagemann's ester
# Hagemann's ester

Hagemann's ester, ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate, is an organic compound that was first prepared and described in 1893 by German chemist Carl Hagemann. The compound is used in organic chemistry as a reagent in the synthesis of many natural products including sterols, trisporic acids, and terpenoids.

## Preparation

### Hagemann's approach

Methylene iodide and two equivalents of ethyl acetoacetate react in the presence of sodium methoxide to form the diethyl ester of 2,4-diacetyl pentane. This precursor is treated with base to induce cyclization. Finally, heat is applied to generate Hagemann's ester.

### Knoevenagel's approach

Soon after Hagemann, Emil Knoevenagel described a modified procedure to produce the same intermediate diethyl ester of 2,4-diacetyl pentane using formaldehyde and two equivalents of ethyl acetoacetate which undergo condensation in the presence of a catalytic amount of piperidine.

### Newman and Lloyd approach

2-Methoxy-1,3-butadiene and ethyl-2-butynoate undergo a Diels-Alder reaction to generate a precursor which is hydrolyzed to obtain Hagemann's ester. By varying the substituents on the butynoate starting material, this approach allows for different C2 alkylated Hagemann's ester derivatives to be synthesized.

### Mannich and Forneau approach

**Original**

Methyl vinyl ketone, ethyl acetoacetate, and diethyl-methyl-(3-oxo-butyl)-ammonium iodide react to form a cyclic aldol product. Sodium methoxide is added to generate Hagemann's ester.

**Variations**

Methyl vinyl ketone and ethyl acetoacetate undergo aldol cyclization in the presence of catalytic pyrrolidinum acetate or Triton B or sodium ethoxide to produce Hagemann's ester. This variant is a type of Robinson annulation.

## Uses

Hagemann's ester has been used as a key building block in many syntheses. For example, a key intermediate for the fungal hormone trisporic acid was made by its alkylation and it has been used to make sterols. Other authors have used it in inverse-electron-demand Diels–Alder reactions leading to sesquiterpene dimers or in reactions forming simple derivatives.

